Multiple injections of human umbilical cord-derived mesenchymal stromal cells through the tail vein improve microcirculation and the microenvironment in a rat model of radiation myelopathy
Background: At present, no effective clinical treatment is available for the late effects of radiation myelopathy.The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy.Methods: An irradiated cervical spinal cord rat model was generated.UC-MSCs were injected through the tail vein at 90, 97, 104 and 111 days post-irradiation.Behavioral tests were performed using the forelimb paralysis scoring system, and histological damage was examined using Nissl staining.The microcirculation in the spinal cord was assessed using von Willebrand factor (vWF) immunohistochemical analysis and laser-Doppler flowmetry.The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the spinal cord.Results: Multiple injections of UC-MSCs through the tail veil decreased the forelimb paralysis, decreased spinal cord histological damage, increased the number of neurons in the anterior horn of the spinal cord, increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, increased the relative magnitude of spinal cord blood flow, down-regulated pro-inflammatory cytokine expression in the serum, and increased anti-inflammatory cytokine expression in the spinal cord.Conclusion: Multiple injections of UC-MSCs via the tail vein in a rat model of radiation myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects.
Radiation myelopathy Endothelial cell Spinal cord blood flow Paracrine system Human umbilical cord-derived mesenchymal stromal cells
Li Wei Jing Zhang Xiu-Bin Xiao Hai-Xing Mai Ke Zheng Wan-Liang Sun Lei Wang Feng Liang Zai-Liang Yang Yuan Liu Yan-Qing Wang Zhi-Fang Li Jia-Ning Wang Wei-Jing Zhang Hua You
Affiliated Hospital of the Academy of Military Medical Sciences,No.8 East Main Street,Fengtai Distri Affiliated Hospital of the Academy of Military Medical Sciences,No.8 East Main Street,Fengtai Distri Affiliated Hospital of the Academy of Military Medical Sciences,No.8 East Main Street,Fengtai Distri Department of Endocrine Surgery,the First Affiliated Hospital of Chongqing Medical University,Chongq Affiliated Hospital of the Academy of Military Medical Sciences,No.8 East Main Street,Fengtai Distri Department of Cardiology & Institute of Clinical Medicine,Hubei University of Medicine,Shiyan,Hubei Research Institute of Surgery,Daping Hospital,Third Military Medical University,Chongqing 400042,Chi